Dipeptidyl peptidase-IV (DPP-IV) is a serine protease that belongs to a group of post-proline/alanine cleaving amino-dipeptidases. DPP-IV catalyzes the release of an N-terminal dipeptide preferentially from proteins with N-terminal penultimate proline or alanine. In vivo administration of synthetic inhibitors of DPP-IV have been shown to improve glycemic control and therefore, such inhibitors have been proposed for the treatment of patients with type II diabetes and related conditions.
Recently, heterocyclic boronic acid inhibitors selective for DPP-IV over DPP-VIII and other related enzymes have been disclosed. In addition, pharmaceutical compositions including such compounds and methods for the use of such compounds are described. Although these applications disclose various methods for the synthesis of heterocylic boronic acid inhibitors, new methods which produce these compounds with improved purity and yield are desirable because of their increasing importance in pharmaceutical formulations and methods of treatment for diabetes and related diseases.